An open-label Phase 2 clinical trial will test the safety and efficacy of IRX-2, an experimental immunology-based cancer therapy, in combination with Keytruda (pembrolizumab) and chemotherapy.
The study is enrolling adults with triple-negative breast cancer (TNBC) — cancers not driven by the hormones progesterone or estrogen, or by the protein HER2 — according to the therapy’s developer, Brooklyn ImmunoTherapeutics.
Already underway at the Providence Cancer Institute, in Portland, Ore., the trial (NCT04373031) is expected to enroll about 30 patients with locally confirmed triple-negative breast cancer who have yet to be treated for advanced non-metastatic TNBC. More information is available here.
IRX-2 is a cell-derived biologic containing multiple immune signaling proteins called cytokines that act on various parts of the immune system. These cytokines promote or enhance an immune response in the area around tumors, known as the tumor microenvironment. It is being tested in various types of cancer, both alone and in combination with other therapies.
One of the components of IRX-2 is interleukin-2 (IL-2), an immune factor that plays a key role in maintaining and restoring immune responses. IL-2 has induced responses in cancer patients, but the human-made (recombinant) formulations have been limited by toxicity and significant immune-related adverse effects (side effects).
Because the therapy is derived from human blood cells, it leads to higher immune activation and dosing at physiological levels, with the goal of reducing potential adverse effects.
In this study, IRX-2 will be evaluated in combination with chemotherapy and the approved immune checkpoint inhibitor Keytruda as a neoadjuvant regimen — meaning, with the goal of shrinking tumors in advance of surgery.
Keytruda works by preventing cancer cells from evading immune attacks by binding to PD-1, a protein found on the surface of immune cells that keeps them from targeting other cells. PD-1 naturally binds to PD-L1, a protein found at higher levels on some types of cancer cells. Blocking this interaction leaves cancer cells with PD-L1 vulnerable to immune attacks.
“IRX-2 is currently being studied in a range of cancer indications, both as a single agent and in combination with other anti-cancer therapies, including checkpoint inhibitors,” Lynn Sadowski Mason, Brooklyn ImmunoTherapeutics’ executive vice president, clinical operations, said in a press release. “We believe that the unique combination of cytokines in IRX-2 can improve outcomes for patients with solid tumor cancers based on its ability to activate the immune system in the tumor microenvironment.”
“We look forward to the results of this clinical trial and to exploring potential new indications in the future,” she added.
This Phase 2 trial comes on the heels of a Phase 1b study (NCT02950259) that showed IRX-2 was well-tolerated, without severe or life-threatening adverse events reported. Moreover, in a Phase 2A clinical trial treating people with head and neck cancers, IRX-2 showed an overall survival benefit.
“In a Phase 1b clinical trial in early-stage breast cancer, IRX-2 was well-tolerated as a single agent with no Grade 3 or 4 toxicities in patients and encouraging signs of activity including upregulation of PD-L1,” said David Page, MD, of the Providence Cancer Institute, the study’s principal investigator.
“These results provide a strong rationale for studying IRX-2 in combination with [Keytruda], an immunotherapy that targets PD-1, and standard of care chemotherapy in triple-negative breast cancer, a disease for which there is an urgent need for new treatment options,” Page said.
In the Phase 2 study, participants will receive alternating regimens of Keytruda plus chemotherapy along with subcutaneous (under-the-skin) injections of IRX-2 twice a day for 10 days. The control arm of the study will test Keytruda plus chemotherapy without IRX-2.
The primary endpoint is pathological Complete Response (pCR) rate, defined as the proportion of participants without residual invasive cancer in the surgically removed tissue and all sampled local lymph nodes following the neoadjuvant therapy at the time of surgery.
Safety and tolerability will be assessed from day one through to a safety follow-up visit, about nine months later.
This study is sponsored by Providence Health & Services, a part of Providence St. Joseph Health, in Oregon. It is being supported in part by a research grant from the investigator-initiated studies program of Merck Sharp & Dohme, a subsidiary of Merck & Co. Merck, known as MSD outside North America, is the developer and owner of Keytruda.